Pharmacomodulation of brain neuromedin U signaling as a potential therapeutic strategy.

Neuromedin U (NMU) belongs to a family of multifunctional neuropeptides that modulate the activity of several neural networks of the brain. Acting via metabotropic receptor NMUR2, NMU plays a role in the regulation of multiple systems, including energy homeostasis, stress responses, circadian rhythms, and endocrine signaling. The involvement of NMU signaling in the central regulation of important neurophysiological processes and its disturbances is a potential target for pharmacological modulation. Number of preclinical studies have proven that both modified NMU analogues such as PASR8-NMU or F4R8-NMU and designed NMUR2 agonists, for example, CPN-116, CPN-124 exhibit a distinct pharmacological activity especially when delivered transnasally. Their application can potentially be useful in the more convenient and safe treatment of obesity, eating disorders, Alzheimer's disease-related memory impairment, alcohol addiction, and sleep disturbances. Accumulating findings suggest that pharmacomodulation of the central NMU signaling may be a promising strategy in the treatment of several neuropsychiatric disorders.

Neuropeptides of the human magnocellular hypothalamus.

Hypothalamic magnocellular nuclei with their large secretory neurons are unique and phylogenetically conserved brain structures involved in the continual regulation of important homeostatic and autonomous functions in vertebrate species. Both canonical and newly identified neuropeptides have a broad spectrum of physiological activity at the hypothalamic neuronal circuit level located within the supraoptic (SON) and paraventricular (PVN) nuclei. Magnocellular neurons express a variety of receptors for neuropeptides and neurotransmitters and therefore receive numerous excitatory and inhibitory inputs from important subcortical neural areas such as limbic and brainstem populations. These unique cells are also densely innervated by axons from other hypothalamic nuclei. The vast majority of neurochemical maps pertain to animal models, mainly the rodent hypothalamus, however accumulating preliminary anatomical structural studies have revealed the presence and distribution of several neuropeptides in the human magnocellular nuclei. This review presents a novel and comprehensive evidence based evaluation of neuropeptide expression in the human SON and PVN. Collectively this review aims to cast a new, medically oriented light on hypothalamic neuroanatomy and contribute to a better understanding of the mechanisms responsible for neuropeptide-related physiology and the nature of possible neuroendocrinal interactions between local regulatory pathways.

Development of the human pancreas and its vasculature - An integrated review covering anatomical, embryological, histological, and molecular aspects.

OBJECTIVES: The aim of this study was to provide a comprehensive overview of the clinically relevant anatomical and histological aspects of the development of the human pancreas, with emphasis on the vascularization of the gland. METHODS: A comprehensive search on the relevant aspects of pancreatic biology was performed through the main electronic databases up to August 2017. Data from all relevant articles was gathered, analyzed and included in this narrative review. RESULTS: This review outlines the main topics on embryology, anatomy, histology, and molecular biology of the microcirculation of the human pancreas. The first part describes in detail the development of the pancreas synthesizing anatomical knowledge with findings of novel molecular studies. The second and third parts give information on the organization of arterial and venous pancreatic circulation. The final part summarizes the most important findings concerning pancreatic microcirculation. All parts taken together create a comprehensive and up-to-date description of the development and organization of the blood supply to the human pancreas. CONCLUSIONS: Detailed knowledge on the physiological development of the pancreas and anatomy of its blood supply play a key role in understanding the pathophysiology of various pancreatic disorders and is crucial for developing novel therapies for pancreatic disorders.

A systematic review and meta-analysis of variations in branching patterns of the adult aortic arch.

OBJECTIVE: The aortic arch (AA) is the main conduit of the left side of the heart, providing a blood supply to the head, neck, and upper limbs. As it travels through the thorax, the pattern in which it gives off the branches to supply these structures can vary. Variations of these branching patterns have been studied; however, a study providing a comprehensive incidence of these variations has not yet been conducted. The objective of this study was to perform a meta-analysis of all the studies that report prevalence data on AA variants and to provide incidence data on the most common variants. METHODS: A systematic search of online databases including PubMed, Embase, Scopus, ScienceDirect, Web of Science, SciELO, BIOSIS, and CNKI was performed for literature describing incidence of AA variations in adults. Studies including prevalence data on adult patients or cadavers were collected and their data analyzed. RESULTS: A total of 51 articles were included (N = 23,882 arches). Seven of the most common variants were analyzed. The most common variants found included the classic branching pattern, defined as a brachiocephalic trunk, a left common carotid, and a left subclavian artery (80.9%); the bovine arch variant (13.6%); and the left vertebral artery variant (2.8%). Compared by geographic data, bovine arch variants were noted to have a prevalence as high as 26.8% in African populations. CONCLUSIONS: Although patients who have an AA variant are often asymptomatic, they compose a significant portion of the population of patients and pose a greater risk of hemorrhage and ischemia during surgery in the thorax. Because of the possibility of encountering such variants, it is prudent for surgeons to consider potential variations in planning procedures, especially of an endovascular nature, in the thorax.

Lateral and posterolateral foraminal variations of the atlas: A meta-analysis.

The lateral (LF) and posterolateral (PLF) foramina are anatomical variants of the atlas. Both variants have been implicated in multiple neurological conditions including vertebrobasilar insufficiency, with symptoms such as dizziness, syncope, auditory and visual disturbances and paresis. The aim of this study was to conduct a systematic meta-analysis on the prevalence and anatomical characteristics of the LF and PLF. An extensive search of the major electronic databases was conducted to identify all studies that reported relevant data on the LF and PLF. No date or language restrictions were applied. Data on the prevalence, type (complete and incomplete), side, gender, and laterality of the LF and PLF, when available, were extracted and pooled into a meta-analysis. A total of 33 studies (n=10,190 subjects) were included in the quantitative analysis. The overall pooled prevalences of complete LF and PLF were 2.6% (95%CI: 2.1-3.1) and 1.2% (95%CI:0.6-2.0), respectively, while the overall pooled prevalence of the incomplete LF was 2.7% (95%CI:1.3-4.4) and the incomplete PLF was 0.7% (95%CI:0.0-1.8). When there was a complete PLF, a contralateral PLF (complete or incomplete) was found in 32.8% of cases. The geographical distribution of both variants was variable. The findings of this study provide an evidence-based foundation of anatomical knowledge of the two variants of the atlas. We recommend that physicians consider the possible role of the LF and PLF during the diagnosis of various neurological disturbances, especially in situations when all other possible explanations for the symptoms have been excluded.

Variations in the Arterial Blood Supply to the Penis and the Accessory Pudendal Artery: A Meta-Analysis and Review of Implications in Radical Prostatectomy.

PURPOSE: The aim of this meta-analysis was to analyze the available literature and provide comprehensive data on the prevalence and variations of the accessory pudendal artery and the 3 types of penile blood supply, including type 1-internal pudendal artery only, type 2-internal pudendal artery and accessory pudendal artery, and type 3-accessory pudendal artery only. MATERIALS AND METHODS: We performed an extensive search of the major databases and identified 23 studies in a total of 4,945 patients suitable for inclusion in this meta-analysis. Studies eligible for inclusion included cadaveric, imaging or intraoperative studies. Extracted data were pooled into a meta-analysis with a random effects model using MetaXL, version 5.0 (EpiGear International, Sunrise Beach, Queensland, Australia). The chi-square test and Higgins I2 statistics were used to assess heterogeneity among included studies. RESULTS: Our findings revealed that the most common type was type 1 with a pooled prevalence estimate of 61.9%, followed by types 2 and 3 with a pooled prevalence estimate of 32.8% and 5.4%, respectively. In our analysis of the accessory pudendal artery the vessel was present in 28.5% of patients. When present, unilateral accessory pudendal arteries were most common (pooled prevalence estimate 72.5%) or they were present on the right or the left side (pooled prevalence estimate 48.0% or 52.0%, respectively). They most commonly originated from the obturator artery and the inferior vesical artery (pooled prevalence estimate 48.9% and 29.6%, respectively). The most common type was apical accessory pudendal arteries (pooled prevalence estimate 60.9%). CONCLUSIONS: A penile blood supply originating at least in part from an accessory pudendal artery represents more than a third of cases. Based on the anatomical findings when an accessory pudendal artery is present, we advocate attempted preservation of the vessel during radical prostatectomy to best maintain the penile arterial blood supply, especially in patients with type 3 or in older patients with type 2.

The Variable Emergence of the Infrapatellar Branch of the Saphenous Nerve.

The infrapatellar branch of the saphenous nerve (IPBSN) is a cutaneous nerve of the lower limb, which arises distal to the adductor canal. High variability in the emergence, course, branching, termination, and morphometrics of the IPBSN poses an increased risk of injury to the nerve during surgical interventions on the anteromedial aspect of the knee. The aim of this study was to describe the anatomical characteristics of the IPBSN. This study utilized cadaveric (n = 100) and ultrasonography (n = 30) assessments, and meta-analysis. In the cadaveric study, the presence of IPBSN and its emergence mode in relation to the sartorius muscle (SaM) was determined (type A-anterior; type B-posterior; type C-penetrating the SaM). Ultrasonography examinations were conducted on healthy volunteers to determine the presence and mode of the emergence of the nerve. Finally, from electronic databases searching, all studies reporting the IPBSN emergence data were pooled into a meta-analysis. The mean distance between the medial border of the patellar ligament (MBPL) and the IPBSN at the level of the patellar apex (PA) was also analyzed in the cadaveric, ultrasonography, and meta-analysis portions of the study. Six studies (n = 336 limbs), including the present cadaveric study, were pooled into the meta-analysis of emergence. The most prevalent IPBSN emergence mode was type C (42.9%) followed by type B (41.9%) and type A (15.4%). In the ultrasonography assessment, type A was found to be the most common (82.8%). The mean distance between the MBPL and the IPBSN at the level of the PA was 4.89 ± 0.22 cm, and 5.57 ± 0.91 cm, for the cadaveric and meta-analysis studies combined, and the ultrasonography assessment, respectively. This multimodality study shows that the most common type of IPBSN emergence is type C. The horizontal distance between the MBPL and the IPBSN at the level of the PA is usually between 4.5 and 5.6 cm. Understanding the anatomy of IPBSN emergence is crucial for orthopedic surgeons to minimize the risks of iatrogenic nerve injury during surgical procedures in the region.

The Anastomoses of the Recurrent Laryngeal Nerve in the Larynx: A Meta-Analysis and Systematic Review.

OBJECTIVES: The recurrent laryngeal nerve and its branches form a great variety of anastomoses. These nerve communications can alter the innervation patterns of the laryngeal muscles and can affect both the diagnosis and treatment of paralyzed vocal cords. The aim of this study was to assess the prevalence and anatomical characteristics of the laryngeal nerve connections, and to review their function and clinical significance. STUDY DESIGN: Meta-analysis and systematic review. METHODS: The major electronic databases were thoroughly searched to identify all studies reporting data on the anastomoses of the laryngeal nerves. Data on the prevalence of each type of anastomosis were extracted and pooled into a meta-analysis using MetaXL version 3.0 (EpiGear International Pty. Ltd., Wilston, Queensland, Australia). RESULTS: Twenty-two cadaveric studies (n = 1404 hemilarynges) were included in the meta-analysis. The two most common communications were Galen's anastamosis and the arytenoid plexus. The pooled prevalence estimate for Galen's anastamosis was 76.7% (95% confidence interval [CI]: 59.0-90.0), of which the single trunk type was most common (92.3%). The arytenoid plexus had a pooled prevalence estimate of 79.7% (95% CI: 41.1-100). CONCLUSIONS: Owing to the high prevalences and variability of nerve connections in the larynx, detailed anatomical knowledge of these anastomoses can be crucial for the accurate interpretation of laryngoscopy results, reducing iatrogenic injury during surgical procedures, and facilitating the development of novel strategies for treating laryngeal paralyses.

The origin of the medial circumflex femoral artery: a meta-analysis and proposal of a new classification system.

Background and Objectives. The medial circumflex femoral artery (MCFA) is a common branch of the deep femoral artery (DFA) responsible for supplying the femoral head and the greater trochanteric fossa. The prevalence rates of MCFA origin, its branching patterns and its distance to the mid-inguinal point (MIP) vary significantly throughout the literature. The aim of this study was to determine the true prevalence of these characteristics and to study their associated anatomical and clinical relevance. Methods. A search of the major electronic databases Pubmed, EMBASE, Scopus, ScienceDirect, Web of Science, SciELO, BIOSIS, and CNKI was performed to identify all articles reporting data on the origin of the MCFA, its branching patterns and its distance to the MIP. No data or language restriction was set. Additionally, an extensive search of the references of all relevant articles was performed. All data on origin, branching and distance to MIP was extracted and pooled into a meta-analysis using MetaXL v2.0. Results. A total of 38 (36 cadaveric and 2 imaging) studies (n = 4,351 lower limbs) were included into the meta-analysis. The pooled prevalence of the MCFA originating from the DFA was 64.6% (95% CI [58.0-71.5]), while the pooled prevalence of the MCFA originating from the CFA was 32.2% (95% CI [25.9-39.1]). The CFA-derived MCFA was found to originate as a single branch in 81.1% (95% CI [70.1-91.7]) of cases with a mean pooled distance of 50.14 mm (95% CI [42.50-57.78]) from the MIP. Conclusion. The MCFA's variability must be taken into account by surgeons, especially during orthopedic interventions in the region of the hip to prevent iatrogenic injury to the circulation of the femoral head. Based on our analysis, we present a new proposed classification system for origin of the MCFA.

Iulius Casserius: revolutionary anatomist, teacher and pioneer of the sixteenth and seventeenth century.

The demand for anatomical illustrations in the early modern period coincided with a scientific revolution. Starting out as a servant, Iulius Casserius became a great anatomist, who challenged the Galenic doctrine. The aim of this paper is to honor his memory and recreate the stylism of his anatomical illustrations. Online databases were searched for articles and original works. A medical graphic designer then recreated the figures presented in the article. Casserius was born around 1552. After moving to Padua, he served Fabricius in performing dissections. Obtaining his medical degree, he began working as an anatomical dissector and surgeon, later giving private anatomy lectures to students. He published De Vocis Auditusque and Pentaestheseion, and then became the lecturer of Surgery. In 1616, Casserius started his first Anatomy course and then died suddenly, at the height of his career. From the sixteenth century, illustrative techniques began focusing less upon artistry in favor of precise depictions of anatomical structures. Fabricius is considered to have used a strict scientific approach to illustrations for the first time. Anatomists of subsequent generations would still frequently use artistry in illustrations. Despite Casserius' mixed accuracy and artistry, his plates mark a new epoch in anatomic representation. Casserius left numerous eponyms and depicted, for the first time, many anatomical structures. Reprints in textbooks in the centuries following show convincing evidence of his success. Casserius contributed to medical education by taking the theatricality out of anatomy. Our article is a tribute to Casserius's achievements and depicts the revolution brought forth by a pioneer of his times.

Median and ulnar nerve anastomoses in the upper limb: A meta-analysis.

INTRODUCTION: The most frequently described anomalous neural connections between the median and ulnar nerves in the upper limb are: Martin-Gruber anastomosis (MGA), Marinacci anastomosis (MA), Riche-Cannieu anastomosis (RCA), and Berrettini anastomosis (BA). The reported prevalence rates and characteristics of these anastomoses vary significantly between studies. METHODS: A search of electronic databases was performed to identify all eligible articles. Anatomical data regarding the anastomoses were pooled into a meta-analysis using MetaXL 2.0. RESULTS: A total of 58 (n = 10,562 upper limbs) articles were included in the meta-analysis. The pooled prevalences were: MGA, 19.5% (95% confidence interval [CI], 16.2%-23.1%); MA, 0.7% (95% CI, 0.1%-1.7%); RCA, 55.5% (95% CI, 30.6%-79.1%); and BA, 60.9% (95% CI, 36.9%-82.6%). The results also showed that MGA was more commonly found unilaterally (66.8%), on the right side (15.7%), following an oblique course (84.8%), and originating from the anterior interosseous nerve with a prevalence of 57.6%. CONCLUSIONS: As anastomoses between the median and ulnar nerves occur commonly, detailed anatomical knowledge is essential for accurate interpretation of electrophysiological findings and reducing the risk of iatrogenic injuries during surgical procedures. Muscle Nerve 54: 36-47, 2016.

Anatomical variations of the formation and course of the sural nerve: A systematic review and meta-analysis.

INTRODUCTION: The sural nerve (SN) is a sensory nerve in the lower extremity which branches to supply the skin on the distal posterolateral third of the lower limb. Typically, the medial sural cutaneous nerve (MSCN) and the peroneal communicating nerve (PCN) unite to form the SN. Other variations in the formation, course, and morphometry of the SN have also been described in the literature. OBJECTIVE: To study anatomical variations in the formation and course of the SN and establish a new classification system for formation patterns of the SN. METHODS: A systematic search of all major databases identified articles that studied the prevalence of variations in the formation of the SN. No date or language restrictions were set. Anatomical data was extracted according to our new classification system where the SN is formed by: union of the MSCN and the PCN (Type 1); union of the MSCN and the Lateral Sural Cutaneous Nerve (LSCN) (Type 2); continuation of the MSCN with absent PCN (Type 3); the PCN alone (Type 4); the LSCN (Type 5); or the Sciatic Nerve (SCN) directly (Type 6). Pooled prevalence rates were calculated using MetaXL 2.0. RESULTS: A total of 39 studies (n=3974 limbs) were included in the meta-analysis. The most common patterns were Type 1, Type 3, and Type 2 with a pooled prevalence of 51.5% (95% CI: 0.293-0.591), 31.2% (95% CI: 0.143-0.410), and 13.8% (95% CI: 0.035-0.234), respectively. The rest of the patterns were rare, with pooled prevalence of Types 4, 5, and 6 calculated to be 1.8% (95% CI: 0-0.063), 1.1% (95% CI: 0-0.050), and 0.7% (95% CI: 0-0.041), respectively. In 83.7% (95% CI: 0.765-0.899) of limbs, the site of union was in the lower half of the lower extremity. The pooled mean length of the SN from the formation to the lateral malleolus was 14.78 (±5.76) cm, while the mean diameter of the SN was 0.28 (±0.03) cm. CONCLUSIONS: Anatomical variations in the formation and course of the SN are common in the population. Clinicians, especially surgeons, should be aware of these variations to avoid iatrogenic injury to the nerve during operative procedures.